Featured Research

from universities, journals, and other organizations

Class of RNA molecules protects germ cells from damage

Date:

November 15, 2012

Source:

University of Pennsylvania

Summary:

Passing one's genes on to the next generation is a mark of evolutionary success. So it makes sense that the body would work to ensure that the genes the next generation inherits are exact replicas of the originals. Biologists have now identified one way the body does exactly that.

Passing one's genes on to the next generation is a mark of evolutionary success. So it makes sense that the body would work to ensure that the genes the next generation inherits are exact replicas of the originals.

Related Articles

New research by biologists at the University of Pennsylvania School of Veterinary Medicine has now identified one way the body does exactly that. This protective role is fulfilled in part by a class of small RNA molecules called pachytene piwi-interacting RNAs, or piRNAs. Without them, germ-cell development in males comes to a halt. Because these play such an important role in allowing sperm to develop normally, the research indicates that defects in these molecules or the molecules with which they interact may be responsible for some cases of male infertility.

Jeremy Wang, an associate professor of developmental biology and director of the Center for Animal Transgenesis and Germ Cell Research at Penn Vet, and Ke Zheng, a postdoctoral researcher in Wang's lab, authored the study, which appears in PLoS Genetics.

Scientists know of 8 million different piRNAs in existence; they are the most abundant type of small non-coding RNA. The molecule piRNA gets its name because it forms complexes with piwi proteins. Earlier work had indicated that these piwi-piRNA complexes suppress the activity of transposable elements or "jumping genes," which are stretches of DNA that can change position and cause potentially damaging genetic mutations. These sequences are also known as transposons.

"There are about 50 human diseases caused by transposable elements, so it's important for the body to have a way to try to repress them," Wang said.

This transposon-suppressing activity had been confirmed in a group of piRNAs called pre-pachytene piRNAs, which are expressed before meiosis, the unique process by which germ cells divide. But Zheng and Wang wanted to investigate if a separate group of piRNAs that emerge during meiosis, called pachytene piRNAs, were also required for "silencing" transposons.

Working in male mice, the researchers manipulated an enzyme called MOV10L1, which is known to interact with piwi proteins and is believed to help produce piRNA molecules. They created a mutant mouse in which they could selectively inactivate MOV10L1 at specific stages before, during and after meiosis. The mice that lost the function of MOV10L1 before or at the pachytene stage of meiosis were sterile. When Zheng and Wang examined their germ cells more closely, they found that spermatogenesis had apparently come to a halt at the post-meiotic stage: Early stages of the germ cells were present, but the mice completely lacked mature sperm.

Further experiments allowed Zheng and Wang to pinpoint that MOV10L1 was playing a critical role at the pachytene stage. MOV10L1 mutants lacked pachytene piRNAs, but their levels of pre-pachytene piRNAs were unaffected, as the mutation was "turned on" after they had already been produced.

The researchers also found that, in the MOV10L1 mutants, piwi proteins congregated together along with mitochondria, suggesting that mitochondria may be involved in the generation or organization of pachytene piRNAs. Furthermore, the spermatids, or early-stage sperm, of the mutants had severe DNA damage. While the researchers suspected that the damage may have been caused because of transposons that had been freed from repression in the absence of piRNAs, they actually found that two common transposable elements were not de-repressed in the mutants. They also found a build-up of pachytene piRNA precursors in the testes of the mutants. Their findings raise the possibility that there is another mechanism by which damage occurs.

"It could be the accumulation of precursor molecules is causing some of the damage," Wang said.

This new function for MOV10L1, in playing an essential role in producing pachytene piRNAs, gives researchers a greater understanding of germ-cell development.

"This is the first time we've shown that pachtyene piRNA is required for maintaining genome integrity in the post-meiotic germ cells," Wang said. "It turns out that MOV10L1 is a master regulator of the piRNA pathway and is required for the production of all piRNAs, both pre-pachytene and pachytene."

Any disruptions to this "master regulator" role, therefore, could lead to problems.

"I think we're just beginning to appreciate the significance of this pathway," Wang said. "Mutations at various points in the pathway could lead to infertility."

This research was supported by the National Institutes of Health's National Institute of Child Health and Human Development.

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015 — New assays can detect malaria parasites in human blood at very low levels and might be helpful in the campaign to eradicate malaria, reports a new study. An international team led by Ingrid Felger, ... full story

Mar. 3, 2015 — Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015 — No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015 — Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015 — Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015 — Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015 — Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015 — Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015 — Although sedatives are often administered before surgery, a randomized trial finds that among patients undergoing elective surgery under general anesthesia, receiving the sedative lorazepam before ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) — After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) — Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) — A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

Feb. 2, 2015 — A specific mechanism by which a parent can pass silenced genes to its offspring has been uncovered by researchers for the first time. Importantly, the team found that this silencing could persist for ... full story

May 21, 2013 — How does the bacterium Shigella -- the cause of a deadly diarrheal disease -- detect that it's in a human host? Scientists have found that a biological "RNA thermometer" monitors ... full story

Oct. 8, 2012 — Malfunctioning of the mitochondria can lead to metabolic disorders in the person affected. Furthermore, mutations in the mitochondrial DNA (mtDNA) are causing muscle weakness, neurodegenerative ... full story

Jan. 12, 2012 — Continuing a series of groundbreaking discoveries begun in 2010 about the genetic causes of the third most common form of inherited muscular dystrophy, scientists have identified the genes and ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.